PubMed ID:
21355061
Public Release Type:
Journal
Publication Year: 2011
Affiliation: Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
DOI:
https://doi.org/10.1681/ASN.2010060598
Authors:
Florez JC,
Coresh J,
Coresh J,
Kestenbaum B,
Boerwinkle E,
Boerwinkle E,
Arking DE,
Shlipak MG,
Shlipak MG,
Aasarød K,
Akylbekova E,
Arnlöv J,
Aspelund T,
Aspelund T,
Atkinson EJ,
Aulchenko YS,
Badola S,
Bakker SJ,
Baumert J,
Beckmann JS,
Bergmann S,
Biffar R,
Blankenberg S,
Boban M,
Bochud M,
Böger CA,
Böger CA,
Borecki I,
Bull SB,
Campbell H,
Campbell H,
Campbell S,
Cavalieri M,
Chasman DI,
Chen MH,
CKDGen Consortium,
Coassin S,
Cupples LA,
Curhan G,
de Andrade M,
de Boer I,
de Boer IH,
Dehghan A,
Devuyst O,
Dreisbach AW,
Egan J,
Eiriksdottir G,
Eiriksdottir G,
Ellinghaus D,
Endlich K,
Endlich K,
Feitosa M,
Felix JF,
Ferrucci L,
Ferrucci L,
Fox CS,
Fox CS,
Franceschini N,
Fuchsberger C,
Fuchsberger C,
Gao X,
Giallauria F,
Glazer NL,
Glazer NL,
Gudnason V,
Gudnason V,
Gyllensten U,
Hallan S,
Haritunians T,
Haritunians T,
Harris TB,
Harris TB,
Hastie ND,
Hastie ND,
Hayward C,
Heid IM,
Heid IM,
Hernandez D,
Hofman A,
Hwang SJ,
Hwang SJ,
Igl W,
Illig T,
Illig T,
Imboden M,
Ingelsson E,
Isaacs A,
Johansson Å,
Johnson AD,
Johnson AD,
Kao WH,
Kao WH,
Kardia SL,
Kedenko L,
Ketkar S,
Klopp N,
Koenig W,
Koenig W,
Kolcic I,
Kollerits B,
Köttgen A,
Köttgen A,
Krämer BK,
Krämer BK,
Kramer H,
Kroemer HK,
Kroemer HK,
Kronenberg F,
Kutalik Z,
Launer LJ,
Launer LJ,
Leak TS,
Li M,
Li M,
Liu CT,
Liu Y,
Lohman K,
Loos RJ,
Luan J,
Lumley T,
Lumley T,
Lu X,
Mägi R,
Meigs JB,
Meisinger C,
Metter J,
Minelli C,
Minelli C,
Mitchell BD,
Mitchell BD,
Mooser V,
Mychaleckyj JC,
Nauck M,
Navis G,
O'Connell JR,
O'Connell JR,
Olden M,
Olden M,
Oostra BA,
O'Seaghdha CM,
Paré G,
Parker AN,
Parsa A,
Parsa A,
Paterson NJ,
Pattaro C,
Pattaro C,
Paulweber B,
Peralta CA,
Polasek O,
Polasek O,
Pramstaller PP,
Pramstaller PP,
Prokopenko I,
Province M,
Psaty BM,
Psaty BM,
Rampersaud E,
Reilly M,
Rettig R,
Rettig R,
Ridker PM,
Rivadeneira F,
Rotter JI,
Rudan I,
Rudan I,
Schmidt H,
Schmidt R,
Schreiber S,
Shuldiner AR,
Shuldiner AR,
Singleton A,
Siscovick D,
Siscovick DS,
Skorpen F,
Smith AV,
Smith AV,
Stracke S,
Struchalin M,
Stumvoll M,
Syvänen AC,
Tanaka T,
Tanaka T,
Teumer A,
Teumer A,
Tin A,
Tönjes A,
Townsend RR,
Turner ST,
Uitterlinden AG,
van der Harst P,
van Duijn CM,
Vitart V,
Vitart V,
Völker U,
Vollenweider P,
Völzke H,
Völzke H,
Waeber G,
Wareham NJ,
Waterworth D,
Wichmann HE,
Wichmann HE,
Wild SH,
Wilson JF,
Witteman JC,
Wright AF,
Yang Q,
Yang Q,
Zaboli G,
Zemunik T,
Zgaga L,
Zhao JH,
Zillikens MC
Studies:
Diabetes Control and Complications Trial
Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.